Volume 4, Issue 3, September – October 2010; Article 005
ISSN 0976 – 044X
A SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM (SMEDDS)
1
Maulik J. Patel1, Sanjay S. Patel1, Natvarlal M. Patel1, Madhabhai M. Patel2
2
Shri B. M. Shah College of Pharmaceutical Education and Research, Modasa, Kalol Institute of Pharmacy, Kalol, India.
*Email: maulik2121@yahoo.co.in
ABSTRACT
The oral delivery of lipophilic drugs presents a major challenge because of the low aqueous solubility of such compounds. Selfmicroemulsifying drug delivery systems (SMEDDSs) have gained exposure for their ability to increase solubility and bioavailability of
poorly soluble drugs. SMEDDS, which are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants, can be used for
the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. SMEDDS can be orally
administered in soft or hard gelatin capsules and form fine relatively stable oil-in-water (o/w) emulsions upon aqueous dilution owing
to the gentle agitation of the gastrointestinal fluids. The efficiency of oral absorption of the drug compound from the SMEDDS depends
on many formulation−related parameters, such as surfactant concentra on, oil/surfactant ra o, polarity of the emulsion, droplet size
and charge, all of which in essence determine the self-emulsification ability. Thus, only very specific pharmaceutical excipient
combinations will lead to efficient self-microemulsifying systems. Although many studies have been carried out, there are few drug
products on the pharmaceutical market formulated as SMEDDS confirming the difficulty of formulating hydrophobic drug compounds
into such formulations. Significant improvement in the oral bioavailability of these drug compounds has been demonstrated for each
case. The fact that almost 40% of the new drug compounds are hydrophobic in nature implies that studies with SMEDDS will continue,
and more drug compounds formulated as SMEDDS will reach the pharmaceutical market in the future.
Keywords: Self-microemulsifying drug delivery systems (SMEDDSs), Lipophillic compound, Droplet Size, Oral Bioavailability.
INTRODUCTION
In modern drug discovery techniques, there has been a
consistent increase in the number of poor water soluble
drug candidate compounds, and currently more than 50%
of new pharmacologically active chemical entities are
lipophillic and exhibit poor water solubility. Various
techniques are use for improve the bioavailability of
those drug like salt formation, pH change, β-cyclodextrin
complex, microemulsion etc. Self-microemulsifying drug
delivery (SMEDDS) is the one of the method for the
improvement of oral bioavailability. SMEDDS are class of
emulsion that has received particular attention as a
means of enhancing oral bioavailability of poorly
absorbed drugs. These systems are essentially mixes of oil
and surfactant (sometimes with added co surfactant) that
form emulsion on mixing with water with little or no
energy input.
SMEDDS or self-emulsifying oil formulations (SEOF) are
defined as isotropic mixtures of natural or synthetic oils,
solid or liquid surfactants, or alternatively, one or more
hydrophilic solvents and co-solvents/surfactants. Upon
mild agitation followed by dilution in aqueous media,
such as GI fluids, these systems can form fine oil-in-water
(o/w) emulsions or microemulsions. Self-emulsifying
formulations spread readily in the GI tract, and the
digestive motility of the stomach and the intestine
provide the agitation necessary for self-emulsification.
SEDDS typically produce emulsions with a droplet size
between 100 and 300 nm while SMEDDS form
transparent microemulsions with a droplet size of less
than 50 nm. When compared with emulsions, which are
sensitive and metastable dispersed forms, SMEDDS are
physically stable formulations that are easy to
manufacture. Thus, for lipophilic drug compounds that
exhibit dissolution rate-limited absorption, these systems
may offer an improvement in the rate and extent of
absorption and result in more reproducible blood-time
profiles.1
The development of SMEDDS may be traced back to the
pesticide industry whereby many herbicides are highly
lipophilic and may not be prepared as concentrated
aqueous solution. As concentrates are necessary for ease
of transportation, it was necessary to develop systems
that could be reconstituted prior to spraying without the
need for elaborate mixing equipment. The herbicides
were therefore dissolved in organic solvents containing
surfactant that could then be emulsified by simple mixing
with water. The concept of using such systems for
pharmaceutical purpose was initially developed by group
of Groves. Therefore aspect of formulation of the
SMEDDS is to improve the bioavailability of the
pharmaceutical product. 2
Mechanism of self-emulsification
The mechanism by which self-emulsification occurs is not
yet well understood. Nevertheless, it has been suggested
that self-emulsification takes place when the entropy
change favoring dispersion is greater than the energy
required to increase the surface area of the dispersion.
The free energy of a conventional emulsion formulation is
a direct function of the energy required to create a new
surface between the oil and water phases. The two
phases of the emulsion tend to separate with time to
reduce the interfacial area and thus the free energy of the
system. The conventional emulsifying agent stabilizes
emulsion resulting from aqueous dilution by forming a
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Volume 4, Issue 3, September – October 2010; Article 005
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monolayer around the emulsion droplets, reducing the
interfacial energy and forming a barrier to coalescence.
On the other hand, emulsification occurs spontaneously
with SEDDS because the free energy required to form the
emulsion is either low and positive or negative. It is
necessary for the interfacial structure to show no
resistance against surface shearing in order for
emulsification to take place. The ease of emulsification
was suggested to be related to the ease of water
penetration into the various LC or gel phases formed on
the surface of the droplets. The interface between the oil
and aqueous continuous phases is formed upon addition
of a binary mixture. This is followed by the solubilization
of water within the oil phases as a result of aqueous
penetration through the interface. This will occur until the
solubilization limit is reached close to the interphase.
Further aqueous penetration will loaded to the formation
of the dispersed LC phase. In the end, everything that is in
close proximity with the interface will be LC, the actual
amount of which depends on the surfactant
concentration in the binary mixture. Thus, following
gentle agitation of the self-emulsifying system, water will
rapidly penetrate into the aqueous cores and lead to
interface disruptions and droplet formation. As a
consequence of the LC interface formation surrounding
the oil droplets, SEDDS become very stable coalescence.
Detailed studies have been carried out to determine the
involvement of LC phase in the emulsion formation
process. Also, particle size analysis and low frequency
dielectric spectroscopy (LFDS) were utilized to examine
the self-emulsifying properties of a series of lmwitor 742
(a mixture of mono- and diglycerides of capric acids)/
Tween 80 system. The results suggested that there might
be a complex relationship between LC formation and
emulsion formation. Moreover, the presence of the drug
compound may alter the emulsion characteristics,
probably by interacting with the LC phase. Nevertheless,
the correlation between the LC formation and
spontaneous emulsification has still not been
1
established.
physical stability and ability to be delivered in standard
soft gelatin capsules.
Improvement of oral absorption by SMEDDS
The release of the drug compound from SMEDDS takes
place upon its partitioning into the intestinal fluids during
droplet transport and disintegration along the GI tract. It
was proposed that two main factors, small particle size
and polarity of the resulting oil droplets determine the
efficient release of the drug compound from SMEDDS. In
o/w microemulsions, however, the impact of the polarity
of the oil droplets is not very significant because the drug
compound reaches the capillaries incorporated within the
oil droplets.
Many studies carried out in animals for the assessment of
the oral bioavailability of hydrophobic drugs formulated
in o/w emulsions indicated better absorption profiles but,
the use of these systems is limited due to their poor
physical stability and the large volumes needed. Thus,
SMEDDS may be a promising alternative to orally
administered emulsions because of their relatively high
A higher bioavailability of hydrophobic drugs
incorporated in SMEDDS was reported earlier. A study
carried out in non-fasting dogs for the assessment of the
oral bioavailability of a lipophilic naphthalene derivative
formulated in SMEDDS demonstrated three−fold higher
values in Cmax and AUC as compared to other dosage
forms. In another study done on rats, the oral
bioavailability of the anti-inflammatory drug ontazolast
was substantially improved when this lipophilic drug was
administered in a lipid based formulation, such as
emulsion, glyceryl oleate (Peceol) solution, and SMEDDS
in comparison to the suspension formulation. A multiple
dosage study was conducted on humans diagnosed with
HIV infection who were given orally an HIV protease
inhibitor either as a SMEDDS or as an elixir. Greater AUC
values in addition to higher Cmax and Cmin values were
reported for patients given the SMEDDS as compared to
the ones given the elixir.1
Physicochemical properties for the selection of drug
Poorly water soluble drugs are a broad class of drugs that
differ significantly in physicochemical properties, so it
would be useful if there were practical guidelines to help
identify the most appropriate formulation for specific
drugs. High melting point drugs with log P values of about
2 are poorly suited to SEMDDS. At the other end of the
spectrum, lipophilic drugs, such as cinnarizine with log P
values greater than 5, are good candidate for SMEDDS.
Drug incorporation into SMEDDS
Drugs with low aqueous solubility present a major challenge
during formulation as their high hydrophobicity prevents
them from being dissolved in most approved solvents. The
novel synthetic hydrophilic oils and surfactants usually
dissolve hydrophobic drugs to a greater extent than
conventional vegetable oils. The addition of solvents
including ethanol, PG and PEG, may also contribute to the
improvement of drug solubility in the lipid vehicle.
The efficiency of drug incorporation into a SMEDDS is
generally specific to each case depending on the
physicochemical compatibility of the drug/system. In most
cases, there is an interference of the drug with the selfemulsification process up to a certain extent leading to a
change in the optimal oil/surfactant ratio. The efficiency of a
SMEDDS can be altered either by halting charge movement
through the system by direct complexation of the drug
compound with some of the components in the mixture
through its interaction with the LC phase, or by penetration
into the surfactant interfacial monolayer. The interference
of the drug compound with the self-emulsification processs
may result in a change in droplet size distribution that can
vary as a function of drug concentration. It should be
pointed out that emulsions with smaller oil droplets in more
complex formulations are more prone to changes caused by
addition of the drug compound. Hence, the design of an
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optimal SEDDS requires pre-formulation solubility and
phase diagram studies to be conducted.1
illustrating these features is presented in figure 1.8 It
should be noted that not every combination of
components produce microemulsions over the whole
range of possible compositions, in some instances the
extent of microemulsion formation may be very limited.
Construction of phase-diagram
The relationship between the phase behavior of a mixture
and its composition can be captured with the aid of a
phase diagram. Compositional variables can also be
studied as a function of temperature and, pressure,
although with the exception of microemulsions prepared
using supercritical or near critical solvents, or with liquefied
chlorofluorocarbon and HFA propellants, the large
majority of systems are studied under conditions of
ambient pressure. The phase behavior of simple
microemulsion systems comprising oil, water and surfactant
can be studied with the aid of ternary phase diagram in
which each corner of the diagram represents 100% of that
particular component. More commonly however, and
almost always in the case of microemulsions in
pharmaceutical applications, the microemulsion will
contain additional components such as a co surfactant
and/or drug.
Figure 1: Example of Phase Diagram
The Co-surfactant is also amphiphilic with an affinity for
both the oil and aqueous phases and partitions to an
appreciable extent into the surfactant interfacial monolayer
present at the oil-water interface. The Co-surfactant need
not necessarily be capable of forming association
structures in its own right. A wide variety of molecules can
functions also surfactants including non-ionic surfactants,
alcohols, alkanoic acids, alkanediols and alkyl amines.
Surprisingly few studies have examined the effect of drug
on phase behavior, this is despite the fact that large
numbers of drug molecules are themselves surface
active and as such would be expected to influence phase
behavior.3 (Kawakami, 2002)
In the case where four or more components are
investigated, pseudo-ternary phase diagrams are used
where a corner will typically represent a binary mixture
of two components such as surfactant / Co-surfactant,
water /drug or oil / drug. The number of different phases
present for a particular mixture can be visually assessed.
A highly schematic (pseudo) ternary phase diagram
Constructing phase diagrams is time consuming,
particularly when the aim is to accurately delineate a
phase boundary, as the time taken for the system to
equilibrate can be greatly increased as the phase boundary
is approached. Heat and sonication are often used,
particularly with systems containing nonionic surfactants,
to speed up the process. Care must be taken to ensure not
only that the temperature is precisely and accurately
controlled, but also that observations are not made on
metastable system. Clearly, however, time constraints
impose a physical limit on the length of time system can
be left to equilibrate and consequently the elimination of
metastable states can be difficult to ensure in practice,
although centrifugation can be useful to speed up any
separation. Within this region, and indeed other multi
phase regions of the ternary phase diagram,
microemulsions can exist in equilibrium with excess
water or oil phases. These multiphase systems can be
conveniently described using the Winsor classification.3 In
the Winsor classification, the one phase microemulsions
that are generally explored as drug delivery systems are
known as Winsor IV systems.
Microemulsions stabilized by non-ionic surfactants,
especially those based on polyoxyethylene, are very
susceptible to temperature because a decrease in
surfactant solubility occurs with increasing temperature,
and as a result systems stabilized by non-ionic surfactants
or mixtures thereof often have characteristic phase
inversion temperatures (PITs), with the PIT of the
microemulsion varying with a range of experimental
factors including the amount and nature of the oil present
and the nature of the surfactant(s) present. Ternary phase
diagrams were constructed using Capmul PG8 (propylene
glycol monocaprylate) as the oil, Tween 20 (polysorbate
20) and/or Cremophor EL (polyoxyl 35 castor oil) as
surfactants.
Formulation of SMEDDS
SMEDDS formulation containing following components
1) Oil phase
2) Primary surfactant
3) Secondary surfactant (co-surfactant)
4) Co-Solvent
These isotropic systems are usually easier to formulate
than ordinary emulsion. The type of associated structure
formed from these components at particular temperature
depends not only on the chemical nature of each
component but also on their relative concentration.
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Volume 4, Issue 3, September – October 2010; Article 005
1) Oil phase
In order to make SMEDDS systems pharmaceutically
acceptable, it is necessary to prepare such systems by
4
using nontoxic and safe components. Oil from natural
sources and their derivatives, e.g. triglycerides and fatty
acid methyl esters are easily degraded by microorganism
and considered to be harmless to the environment. The
formation of bicontinuous microemulsions with mineral
oils has been intensively investigated in model
5
experiments and for application in industrial products.
An acceptable lipophilic phase for pharmaceutical uses
would be vegetable oils. The extension of a
microemulsion region generally depends on nature of oil.
This is due to differences in oil penetration into the
surfactant layer. 6
ISSN 0976 – 044X
the relative contribution of hydrophilic and hydrophobic
fragments of the surfactant molecule. It accepted that low
HLB (3-6) surfactants are favored for the formation of w/o
microemulsions whereas surfactants with high HLB (818) are preferred for the formation of o/w
microemulsion systems. Ionic surfactants such as sodium
dodecyl sulphate which have HLBs greater than 20, often
require the presence of a co surfactant to reduce their
effective HLB to a value within the range required for
microemulsion formation. In contrast, the CPP relates the
ability of surfactants to form particular aggregates to the
geometry of the molecule itself.
The analysis of film curvature for surfactant association
leading to microemulsion formation has been explained
by Isaraelachvili 3
In terms of the packing ratio, P
Example:
Castor oil, Sunflower oil, Olive oil,
Hydrogenated specialty oils
Seseam oil,
2) Surfactant
A surfactant molecule is formed by two parts with
different affinities for the solvents. One of them has
affinity for water (polar solvents) and the other has for oil
(non-polar solvents). A little quantity of surfactant
molecules rests upon the water-air interface and
decreases the water surface tension value (the force per
unit area needed to make available surface). That is why
the surfactant name: “surface active agent”. 7
Figure 2: Shows structure of surfactant molecule
containing hydrophilic head and hydrophobic tail group.
Surfactants used to stabilize microemulsion system may
be: (i) non-ionic, (ii) zwitterionic, (iii) cationic, or (iv)
anionic surfactants. Combinations of these, particularly
ionic and non-ionic, can be very effective at increasing the
extent of the microemulsion region. Examples of nonionic include polyoxyethylene surfactants such as Brij 35
or sugar esters such as sorbitan monooleat (Span 80). The
use of additional surfactants such as sodium dodecyl
sulfate or sodium deoxycholate significantly improved the
solubilization capacity of the oils, although formulations
free of these surfactants ware also available. These
microemulsion formulations can be administered as a
form of water-in-oil microemulsion or surfactant-oil
mixture, and are expected to convert to oil-in-water
microemulsion in small intestine. 8
Attempts have been made to rationalize surfactant
behavior in terms of the hydrophile-lipophile balance
(HLB), as well as the critical packing parameter (CPP).
Both approaches are fairly empirical but can be a useful
guide to surfactant selection. The HLB takes into account
Figure 3: CPP of surfactant molecule
P = Vo/AoLo
Where VO = partial molar volume of the surfactant
Ao= cross sectional area of the surfactant head group
Lo = maximum length of the surfactant chain
The packing ratio provides a direct measure of HLB and is
influenced by the same factors. The o/w structure are
favored if the effective polar part is more bulky then the
hydrophobic part (P<1), and the interface curves
spontaneously toward water (positive curvature). The
w/o structures are formed, when the interface curves in
the opposite direction (p>1, negative curvature). At zero
curvature, when the HLB balanced (P~1), either
bicontinuous or lamellar structures may form according
to the rigidity of the film.4
Example:
Propylene glycol monocaprylate (Capryol 90)
Polyglycolized glycerides (Gelucire 44/14, 50/13)
Polyoxyl-40 hydrogenated castor oil (Cremophor RH 40)
Oleoyl macrogol-8 glycerides (Labrafil M 1944 CS)
Linoleoyl macrogolglycerides (Labrafil M 2125 CS)
PEG-8 caprylic/capric glycerides (Labrasol)
Polyoxyethylene glyceryl trioleate (Tagat TO)
Polyoxyethylene(20)sorbitan monooleate (Tween 80)
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3) Co-surfactant
Most single-chain surfactants do not lower the oil-water
interfacial tension sufficiently to form microemulsions nor
are they of the correct molecular structure. Further
under certain condition, a combination of oil, water and
surfactant will result in a phase where there are orderly
planes of oil and water separated by monomolecular layer
of surfactant. This type of phase is known as liquid crystal
(lamellar phase). Liquid crystals formation can be detected
by large increase in viscosity. Co-surfactant is added to
further lower the interfacial tension between the oil and
water phase, fluidize the hydrocarbon region of the
9
interfacial-film, and to influence the film curvature.
Typical co-surfactants are short chain alcohols (ethanol to
butanol), glycols such as propylene glycol, medium chain
alcohols, amines or acids. Abe et al (1986) concludes
that the role of co-surfactant is to destroy liquid
crystalline or gel structures that form in place of a
microemulsion phase. They also conclude that cosurfactant free microemulsion in most system cannot be
made except at high temperature. El-Nokaly et al
summarized the role of a Co-surfactant as following: -10
1) Increase the fluidity of the interface
2) Destroy liquid crystalline or gel structure which would
prevent the formation of microemulsion.
3) Adjust HLB value and spontaneous curvature of the
interface by changing surfactant partitioning characteristic
4) Co-solvents
The production of an optimum SEDDS requires relatively
high concentrations (generally more than 30% w/w) of
surfactants. Organic solvents such as, ethanol, propylene
glycol (PG), and polyethylene glycol (PEG) are suitable for
oral delivery, and they enable the dissolution of large
quantities of either the hydrophilic surfactant or the drug in
the lipid base. These solvents can even act as co-surfactants
in microemulsion systems. On the other hand, alcohols and
other volatile co-solvents have the disadvantage of
evaporating into the shells of the soft gelatin, or hard,
sealed gelatin capsules in conventional SEDDS leading to
drug precipitation. Thus, alcohol−free formula ons have
been designed, but their lipophilic drug dissolution ability
1
may be limited.
Characterization of SMEDDS:
Differential scanning calorimetry
Differential scanning calorimetry for SMEDDS can be
determined using DSC 60. Liquid sample and Solid
sample should be placed in the aluminum pan and result
can be recorded. Any type of chemical interaction
should be determined using DSC.11
Fourier transform-infrared spectroscopy
Fourier transform-infrared for SMEDDS can be
determined using FT-IR. Liquid sample should be placed
in the liquid sample holder and result can be recorded.
ISSN 0976 – 044X
Any type of chemical interaction should be determined
using FT-IR. 12
Macroscopic evaluation
Macroscopic analysis was carried out in order to observe
the homogeneity of microemulsion formulations. Any
change in color and transparency or phase separation
occurred during normal storage condition (37±2ºC) was
observed in optimized microemulsion formulation.
Visual assessment
To assess the self-emulsification properties, formulation
(60 mg) was introduced into 100 ml of water in a glass
Erlenmeyer flask at 25°C and the contents were gently
stirred manually. The tendency to spontaneously form a
transparent emulsion was judged as good and it was
judged bad when there was poor or no emulsion
formation. Phase diagram was constructed identifying the
good self-emulsifying region.13
Determination of Self emulsification time
The emulsification time of SMEDDS was determined
according to USP 22, dissolution apparatus 2. 300 mg of
each formulation added drop wise to 500ml purified
water at 37ºC. Gentle agitation was provided by a
standard stainless steel dissolution paddle rotating at 50
rpm. Emulsification time was assessed visually.14
Solubility studies
Unknown amount of selected vehicles was added to each
cap vial containing an excess of drug. After sealing, the
mixture was heated at 40ºC in a water bath to facilitate
the solubilization. Mixing of the systems was performed
using a vortex mixer. Formed suspensions were then
shaken with a shaker at 25ºC for 48 hours. After reaching
equilibrium, each vial was centrifuged at 3000 rpm for 5
minutes, and excess insoluble LOV was discarded by
filtration using a membrane filter (0.45 µm, 13 mm,
Whatman, India). The concentration of drug was then
quantified by U.V.Spectrophotometer.13
Transmittance Test
Stability of optimized microemulsion formulation with
respect to dilution was checked by measuring
Transmittance through U.V. Spectrophotometer (UV-1700
SHIMADZU). Transmittance of samples was measured at
650nm and for each sample three replicate assays
were performed.13
Droplet size determination
It is a precise method for evaluation of stability. Size of
droplet
is
measured
by
photon-correlation
spectroscopy (PSC) with Zetasizer. All measurements
are carried out at scattering angle of 90° and 25°C
temperatures. Prior to measurement, microemulsion is
diluted in two-steps with pure water then it is filtered
through a 0.22um filter just before it is added to
cuvette. In first step it is diluted with equal amount of
water. In second step the mixture is further diluted to
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Volume 4, Issue 3, September – October 2010; Article 005
appropriate concentration for the measurement. That
depends on droplet size (Usually diluted 100-200 times).
15
Zeta potential measurement
Zeta potential for microemulsion was determined using
Zetasizer HSA 3000 (Malvern Instrument Ltd., UK).
Samples were placed in clear disposable zeta cells and
results were recorded. Before putting the fresh sample,
cuvettes were washed with the methanol and rinsed
using the sample to be measured before each
experiment.14
Stability16
Temperature Stability
Shelf life as a function of time and storage temperature
was evaluated by visual inspection of the SMEDDS system at
different time period. SMEDDS was diluted with purified
distilled water and to check the temperature stability of
samples, they were kept at three different temperature
range (2-8°C (refrigerator), Room temperature) and
observed for any evidences of phase separation,
flocculation or precipitation.
Centrifugation
In order to estimate metastable systems, the optimized
SMEDDS formulation was diluted with purified distilled
water. Then microemulsion was centrifuged (Remi
Laboratories, Mumbai, India) at 1000 rpm for 15 minute
at 0°C and observed for any change in homogeneity of
microemulsions.
ISSN 0976 – 044X
Sustain release from SMEDDS
Due to the wide range of structures occurring in them,
SMEDDS display a rich behavior regarding the release of
solubilized material. Thus in. case of O/W microemulsion,
hydrophobic drugs solubilized mainly in the oil droplets,
experience hindered diffusion and are therefore released
rather slowly (depending on the oil/water partitioning of
the substance). Water soluble drugs, on the other hand,
diffuse essentially without obstruction (depending on the
volume fraction of the dispersed phase) and are release
fast. For balanced microemulsions, relatively fast
diffusion and release occur for both water soluble and oil
soluble drugs due to the bicontinuous nature of
microemulsion
"structure".4
Apart
from
the
microemulsion structure, the microemulsion composition
is important for the drug release rate.
Increase the bioavailability of drug
Many of drugs were lipophilic in nature so, it should be
insoluble in water. Lipophilic drug should have low
bioavailability. In SMEDDS, drugs should be combining
with the
oil and make a complex. Oil is easily absorbed
from the gut and increase the solubility of drugs. So
increase the bioavailability of the drug. Ex. Julianto et al,
was increase the 3 fold bioavailability from SEDDS which
is composed of the Tween 80 and palm oil. 18
REFERENCES
1.
Neslihan Gursoy, R. and Benita, S. Self-emulsifying
drug delivery systems (SEDDS) for improved oral
delivery of lipophilic drugs.
Biomedicine &
Pharmacotherapy; 2004; 58; 173–182.
2.
Attwood, A. Colloidal drug delivery systems, In:
Kreutzer, J. (Ecls.) Microemulsions. Marcel Dekker; New
York; 1994; 33-71.
3.
Lawrence, M. J. and Rees, G. D. Microemulsion-based
media as novel drug delivery systems. Adv. Drug
Delivery Rev.; 2000; 45; 89-121.
4.
Kumar, P. and Mital, K. L. Handbook of microemulsion:
Science and Technology. Marcel Dekker, New York,
Basel; 1999.
5.
Lin, S.L.; Menig, J. and Lachman, L. Interdependence of
physiological surfactant and drug particle size on the
dissolution behavior of water-insoluble drugs. J. Pharm.
Sci.; 1968; 2143-2148.
6.
Shford, D. M. and Craig D. Q. M. The emulsification
and solubilization properties of polyglycolysed oils in
self-emulsifying formulations. J. Pharm. Pharmacol.;
2004; 56; 307-316.
7.
Alander, S.; Gennes, P. O. and Taupin C.
Microemulsions and the flexibility of oil /water
interfaces. J. Phys. Chem.. 1982; 86; 2294- 2304.
8.
Kawakami, K. and Yoshikawa, T. Microemulsion
formulation for enhanced absorption of poorly soluble
drug I Prescription design. Journal of Controlled
In vitro release
The quantitative in vitro release test was performed in
900 ml purified distilled water, which was based on USP
24 method. SMEDDS was placed in dialysis bag during the
release period to compare the release profile with
conventional tablet. 10 ml of sample solution was
withdrawn at predetermined time intervals, filtered
through a 0.45 µ membrane filter, dilute suitably and
analyzed spectrophotometrically. Equal amount of fresh
dissolution medium was replaced immediately after
withdrawal of the test sample. Percent drug dissolved at
different time intervals was calculated using the Beer
17
Lambert’s equation.
Applications of SMEDDS
Solubilization in SMEDDS
Owing to their frequently high content oil, as well as of
surfactant, SMEDDS are usually efficient solubilizers of
substances of a wide range of lipophilicity. Thus, the
solubilizing capacity of a w/o microemulsion for water
soluble drugs is typically higher than that of an o/w
microemulsion, while the reverse is true for oil soluble
drugs. Furthermore, the solubilization depends on the
SMEDDS composition.
International Journal of Pharmaceutical Sciences Review and Research
Available online at www.globalresearchonline.net
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ISSN 0976 – 044X
Release; 2002; 81; 65-74.
9.
Ozawa, K.; Olsson, U. and Cawes, A. Oil-induced
structural change in nonionic microemulsions. Journal
of Dispersion Science and Technology; 1986; 22(1); 119124.
10. El-Nokaly, I. and Ravey, J. Solubilization by nonionic
surfactant in the HLB Temperature Range. In:
Micellization, solubilization and Microemulsions, Vol.2
(R.K.Mittal, ed.), Plennum press, New York; 1991; 901911.
(SMEDDS) containing Atorvastatin. Pharmacy and
pharmacology; 2006; 1183-1191.
14. Wei, L.; Li, J.; Guo, L.; Nei, S. and Pan, W. Preparation
and evaluation of SEDDS and SMEDDS containing
Carvedilol. Drug development and industrial
pharmacy; 2005; 31; 785-794.
15. Zhang, P.; Liu, Y.; Feng, N. and Xu, J. Preparation and
evaluation of self-microemulsifying drug delivery
system of oridonin. International journal of
pharmacy; 2007.
11. Taha, E.; Saidan, S.; Samy. A. and Khana, M.
Preparation and in vitro characterization of selfnanoemulsified drug delivery system (SNEDDS) of alltrans-retinol acetate. International journal of
pharmaceutics; 2004; 285; 109–119.
16.
12. Nazzal, S.; Smalyukh, I. I.; Lavrentovich, O. D. and
Khan M. A. Preparation and in vitro characterization
of a eutectic based semisolid self-nanoemulsified
drug delivery system (SNEDDS) of ubiquinone:
mechanism and progress of emulsion formation.
International Journal of Pharmaceutics;2002; 235;
247–265.
17. Kang, B.; Lee, J.; Chon, S.; Jeong, S.; Yuk, S.; Khang, G.;
Lee, H. and Hang Choc S. Development of selfmicroemulsifying drug delivery systems (SMEDDS) for
oral bioavailability enhancement of simvastatin in
beagle dogs. International journal of pharmaceutics;
2004; 274; 65-73.
13. Shen, H. and Zhong, M. Preparation and evaluation of
self-microemulsifying
drug
delivery
systems
Ghosh, P. K.; Umrethia, M. L.; Majethiya, R. J.; and
Murthy, R. S. R. Preparation and Physicochemical
characterisation of caprylocapryl macrogol -8glycerides microemulsion for oral drug delivery. Ars
Pharm; 2004; 45 (3); 353-372.
18. Julianto, T.; Yuen, K. and Noor, A. Improved
bioavailability of vitamin E with a self-emulsifying
formulation. International journal of pharmaceutics;
2000; 200; 53–57.
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